{
  "abstract": "Aged skeletal muscle has a reduced ability to adapt to hypertrophic stimuli concomitant with dysregulation across several molecular layers. Whether altered RNA splicing associates with impaired adaptive potential is not well studied. We hypothesized that aging disrupts the splicing response to involuntary muscle mechanical loading. Using deep short-read Illumina RNA-sequencing (SRS, 60 million read pairs) and third generation Oxford Nanopore long-read RNA-sequencing (LRS) combined with a murine model of acute muscle mechanical overload (MOV), we illustrate how aged muscle has a reduced or possibly delayed potential for isoform switching in response to stress. SRS identified hundreds of genes with isoform switching events in adult MOV relative to sham but only 37 in aged MOV. LRS identified 19 genes (including Cacnb1, Naca, Psap) with true isoform switching in adult MOV and none in aged MOV. A subset of genes showed significant isoform switching without corresponding changes in overall gene expression, suggesting post-transcriptional regulation in response to MOV. These data highlight the importance of analyzing the transcriptome at the isoform level to uncover transcript diversity and \"unseen genes\" that may have unique functions and mechanisms influencing hypertrophic adaptations.",
  "abstract_shown": true,
  "affiliations": [
    "Cell and Molecular Biology Graduate Program, University of Arkansas, Fayetteville, Arkansas, USA.",
    "Molecular Muscle Mass Regulation (M3R) Laboratory, Department of Health, Human Performance, & Recreation, University of Arkansas, Fayetteville, Arkansas, USA.",
    "Department of Biomedical Engineering, University of Arkansas, Fayetteville, Arkansas, USA.",
    "Department of Physiology, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.",
    "Department of Internal Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.",
    "Department of Anatomy, Physiology, and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama, USA.",
    "NextGen Precision Health Initiative, University of Missouri, Columbia, Missouri, USA.",
    "Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, USA.",
    "Department of Medical Pharmacology and Physiology, University of Missouri, Columbia, Missouri, USA."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Pieter J Koopmans",
      "orcid": "0000-0002-4797-5265"
    },
    {
      "affs": [
        2
      ],
      "name": "Abbey L Stokes"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Christopher E Nelson",
      "orcid": "0000-0002-8423-8854"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Yuan Wen",
      "orcid": "0000-0002-3210-1629"
    },
    {
      "affs": [
        5
      ],
      "name": "Ahmed Ismaeel",
      "orcid": "0000-0003-4025-3945"
    },
    {
      "affs": [
        0,
        1,
        6,
        7,
        8
      ],
      "name": "Kevin A Murach",
      "orcid": "0000-0003-2783-7137"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/05kgh9d2wmd9w.bib",
  "cited_by": 0,
  "doi": "10.1111/acel.70761",
  "fulltext_url": "https://europepmc.org/articles/PMC13669657",
  "id": "05kgh9d2wmd9w",
  "issns": [
    "1474-9718",
    "1474-9726"
  ],
  "landing_url": "https://europepmc.org/article/MED/42876144",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7221850421",
  "pdf_url": "https://europepmc.org/articles/PMC13669657?pdf=render",
  "pmcid": "PMC13669657",
  "pmid": "42876144",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/05kgh9d2wmd9w.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42876144",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42876144"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Muscle Physiology and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A Hypertrophic Stimulus Drives Age-Dependent Transcript Isoform Switching With and Without Differential Gene Expression in Skeletal Muscle.",
  "title_text": "A Hypertrophic Stimulus Drives Age-Dependent Transcript Isoform Switching With and Without Differential Gene Expression in Skeletal Muscle.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/05kgh9d2wmd9w",
  "venue": "Aging cell",
  "versions": []
}